C. Bolduc MD, FRCPC and J. Shapiro MD, FRCPC
Division of Dermatology, Faculty of Medicine, University of British Columbia, Vancouver, Canada
Topical immunotherapy with diphencyprone (DPCP) for the treatment of severe alopecia areata has been used since 1983 and is felt to be the treatment of choice by many dermatologists. Although there have been no major side effects reported since its initial use, there remain some unknowns regarding its safety. Because DPCP has at least a 40% success rate for cosmetically acceptable regrowth in extensive alopecia areata, its availability is an important matter for patients with alopecia areata.
topical immunotherapy, diphencyprone, alopecia areata
Topical immunotherapy using diphencyprone (DPCP) is considered by many dermatologists to be the treatment of choice for extensive alopecia areata. Unfortunately, DPCP is not officially approved anywhere mainly because there is not enough evidence to support its safety.
DPCP has been used throughout the world since 1983 for the treatment of extensive (>40%) alopecia areata. It is a compound used topically to induce an allergic contact dermatitis. Its exact mechanism of action is still unknown, but researchers hypothesize that the inflammatory reaction that is created diverts the immune system away from the hair follicle, thereby allowing new hair to grow.
The average response rate varies among patients with alopecia areata, but seems to be around 40% for cosmetically acceptable regrowth1,2. Forty percent of those who respond will maintain a cosmetically acceptable head of hair even 6 months after DPCP has been stopped1,2. The most common side effects are mild eczema, cervical lymphadenopathy and skin pigment changes1,2.
The US FDA is concerned that there are too many unknowns regarding DPCP. However, there are some encouraging data in favour of its safety. DPCP was not detected in the serum or urine of patients treated topically for alopecia areata, and no major side effects have been reported since its initial use.
Because of the safety controversy regarding DPCP, we discuss the issue with our patients before treating them and ask them to sign an informed consent. We have treated more than 200 patients with DPCP over the past 10 years and have had great patient satisfaction with no major side effects3.
|Indication||Treatment of alopecia areata when more than 40% of scalp hair is lost.|
|Technique of application||Sensitization with 2% DPCP followed by weekly application of a lower concentration that will be slowly increased each week until a mild eczema is elicited.|
|Maximum duration of treatment if no response||6 months|
|Initial response||12 weeks|
|Cosmetically acceptable regrowth||24 weeks|
|Overall response rate:|
|Relapse rate||60% at six months in patients who experienced a cosmetically acceptable regrowth.|
Table 1: Summary3
When we contacted the US FDA, they told us they could not release any information concerning a drug that is not approved because it is considered confidential. However, we were able to find out that DPCP appears to have been excluded for the following reasons:
- There is a synthetic precursor and potential contaminant of commercial purified DPCP that is mutagenic in the Ames assay.
- There are unknowns in the toxicology profile such as chronic toxicity, reproductive toxicity and human teratogenicity.
The FDA position is that pharmacies can still carry DPCP and squaric acid dibutyl ester (SADBE), but they cannot publicize across state lines that they have these products.
For physicians in Canada, we have contacted the Health Protection Branch (HPB – Ottawa) and there is, as yet, no formal regulation regarding the use of DPCP. The guidelines suggest that physicians in their office can use DPCP for their own patients, but they must assume liability for any adverse effects.
Although alopecia areata is a medically benign condition, it can cause extreme distress in a large number of patients.
After weighing the pros and the cons, the National Alopecia Areata Foundation and the US FDA are considering the possibility of making DPCP available as an investigational new drug. At this time, a decision has not been made as to whether the investigation will be done in a multi-center study, or by issuing “packets” that will be available to physicians in the US who want to take part. In Canada, once again, this whole process is not mandatory.
Within the next few years, the collection of all combined worldwide data, including Canada, should allow the US FDA and HPB – Ottawa to assess safety issues more accurately in order to ultimately gain full regulatory approval.
- Rokhsar C, Shupack J, Vafai J, Washenik K. Efficacy of topical sensitizers in the treatment of alopecia areata. J Am Acad Derm 39(5 pt 1): 751–61 (1998 Nov).
- Shapiro J, Price VH. Hair regrowth. Therapeutic Agents. Dermatol Clin 16(2): 341–56 (1998 Apr).
- Shapiro J, Bolduc C. Unpublished data (2000).
Skin Cap Spray – In March 2000, HPB-Ottawa announced that Skin-Cap Spray (Cheminova Internacional, Madrid, Spain) was found to contain an undeclared and potent corticosteroid at a class 1 hazard level, and should not be used without medical supervision. The corticosteroid in question in betamethasone-21-butyrate-17-propionate.
Skin-Cap Spray was approved in Canada as an OTC anti-dandruff preparation, but the product was mislabelled to treat seborrheic dermatitis and mislabelled as to the contents.
Dermalabs Inc., the Canadian distributor for this product, has voluntarily initiated a recall. Health Canada is not aware of any reports of illness and has received no complaints associated with the current distribution of this product, which was only recommenced in mid-January 2000. This is the second time HPB-Ottawa has issued a warning about Skin-Cap because it contained an undeclared corticosteroid. The first time was in 1997, when it was found to contain clobetasol, another potent corticosteroid. Skin-Cap is sold in many countries worldwide.
Miralex Skin Cream – Another product that was found to contain an undeclared corticosteroid (clobetasol propionate), and was subsequently withdrawn by HPB-Ottawa is Miralex Skin Cream. It was sold as a corticosteroid-free natural product.
A class action suit has been commenced in British Columbia, Canada, against the distributors of this product. If you or your patients would like to learn more about the class action, contact Mr. Ward Branch at the law firm of Branch MacMaster (604) 654-2966, e-mail <email@example.com>. At this time, the class action is only proposed on behalf of BC residents. However, Mr. Branch indicates that if someone from outside BC comes forward, the action could be expanded to include persons from outside BC.